参附注射液对急性坏死性胰腺炎大鼠肠黏膜屏障保护作用的研究

目的 探讨参附注射液对ANP大鼠肠黏膜屏障的保护作用及机制.方法 雄性Wister大鼠21只,按随机分组法分为对照组、ANP组及参附治疗组(SF组),检测各组血浆MDA、MPO、SOD、TNF-α及小肠组织MDA、NO、MPO含量;免疫组化方法检测小肠组织NF-кB、ICAM-1及iNOS的蛋白表达.结果 ANP组血浆MPO、MDA、SOD、TNF-α量分别为(390.22±24.58)U/L、(41.79±5.68)nmol/L、(108.74±12.98)U/ml和(5.54±0.31)fmol/ml;肠组织MPO、MDA、NO含量分别为(270.96±31.86)U/g湿片、(7.61±2.02)nmol/g port和(51.21±46.98)μmoL/g prot;NF-кB、ICAM-1及iNOS蛋白阳性表达细胞数分别为85.68±7.79、0.218±0.035和0.098±0.016.SF组相对应值分别为(279.68±50.19)U/L、(31.07±3.92)nmoL/L、(123.45±7.94)U/L和(4.82±0.24)fmol/L:(214.46±19.64)U/g湿片、(2.88±1.48)nmol/g port和(20.27±7.92)μmol/g port;19.87±7.88、0.124±0.018和0.069±0.024.各项指标两组间差异均非常显著(P＜0.01).结论 参附注射液对ANP大鼠肠黏膜屏障有保护作用,其机制可能通过抑制NF-кB的表达,减少TNF-α、ICAM-1及iNOS的生成,从而改善肠道微循环,减轻肠组织炎症反应和减少氧自由基所致.     

曲美他嗪对急性肝衰竭小鼠肝组织NOX2和NOX4表达的影响

目的 探讨曲美他嗪对急性肝衰竭小鼠肝组织NOX2和NOX4表达的影响。方法 随机将65只C57BL/6小鼠分为对照组、模型组、小、中、大剂量曲美他嗪处理组和还原型谷胱甘肽处理组,除模型组15只外,其他组均为10只。采用D-氨基半乳糖联合脂多糖腹腔注射建立急性肝衰竭模型。取肝组织匀浆检测丙二醛(MDA)和过氧化物酶(CAT)含量,采用RT-PCR法和Western blot法分别检测肝组织还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶( NOX2/4) mRNA水平和蛋白表达。结果 模型组血清ALT、AST和肝匀浆MDA水平分别为(121.4±3.7)U/L、(208.9±27.4)U/L和(51.0±20.5)nmol/mg,均显著高于对照组【分别为(35.3±3.2)U/L、(49.9±4.4)U/L和(14.1±5.2)nmol/mg,P＜0.05】,而模型组肝匀浆CAT水平为(51.7±16.8)U/mg,显著低于对照组【(110.2±33.7)U/mg,P＜0.05】;模型组NOX2/4 mRNA和蛋白相对水平分别为(8.2±2.0)/(1.2±0.1)和(2.6±0.1)/(1.3±0.1),均显著高于对照组【分别为(1.0±0.2)/(0.5±0.1)和(1.0±0.1)/(0.4±0.1),P＜0.05】,中、大剂量曲美他嗪处理组血清ALT和AST及肝匀浆MDA水平分别为(86.4±1.00)U/L、(154.0±6.2)U/L和(22.5±1.9)nmol/mg及(81.1±1.5)U/L、(134.7±5.3)U/L和(20.1±3.7)nmol/mg,均显著低于模型组【分别为(121.4±3.7)U/L、(208.9±27.4)U/L和(51.0±20.5)nmol/mg,P＜0.05】,肝匀浆CAT水平分别为(99.4±15.5)和(102.3±15.5),均显著高于模型组【(51.6±16.8),P＜0.05】;肝组织NOX2/4 mRNA及蛋白相对表达量分别为(5.6±0.2)/(0.7±0.0)和(5.2±1.4/0.6±0.1)及(1.7±0.2)/(0.7±0.2)和(1.5±0.1)/(0.6±0.2),均显著低于模型组【(8.2±2.0)/(1.2±0.1)和(2.6±0.1)/(1.3±0.1),P＜0.05】。结论 曲美他嗪可能通过下调肝组织NOX2/4表达减轻氧化应激损伤,改善D-Galn/LPS诱导的急性肝衰竭小鼠肝损伤。     

蓝莓花青素干预肝硬化大鼠肝组织凋亡蛋白表达的变化*

目的 研究蓝莓花青素干预肝硬化大鼠肝组织凋亡蛋白表达的变化。方法 随机将30只大鼠分为对照组、模型组和实验组。采用二乙基亚硝胺腹腔注射法制备肝硬化模型,在其中一组给予蓝莓花青素灌胃干预,在实验第8周末,取血和肝组织。采用Western blot法检测肝组织c-caspase-3、Bax和Bcl2蛋白表达,取肝组织匀浆检测丙二醛(MDA)和超氧化物歧化酶(SOD)含量。结果 组织病理学检查提示,肝硬化模型制备成功;模型组动物血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、肿瘤坏死因子-α(TNF-α)和转化生长因子-β(TGF-β)水平分别为(579.87±20.37)U/L、(428.58±18.25)U/L、(2.56±0.18)ng/L和(2.12±0.15)ng/L,显著高于对照组 [分别为(102.47±3.25)U/L、(104.45±3.87)U/L、(0.81±0.05)ng/L和(0.92±0.07)ng/L,P<0.05],而经过蓝莓花青素处理后,动物血清上述指标显著降低【分别为(371.89±14.72)U/L、(148.71±6.34)U/L、(1.73±0.11)ng/L和(1.45±0.12)ng/L,P<0.05],模型动物血清白蛋白水平为(30.69±2.58)g/L,显著低于对照组【(37.68±3.08)g/L,P<0.05】, 蓝莓花青素处理组升高至【(34.71±3.34)g/L,P<0.05];模型组肝组织匀浆MDA水平为(0.49±0.11)μmol/L,显著高于对照组【(0.06±0.01)μmol/L,P<0.05】,SOD水平为(0.34±0.09)U/mg,显著低于对照组【(0.98±0.21)U/mg,P<0.05】,而蓝莓花青素处理组肝组织匀浆MDA水平显著降低至【(0.17±0.03)μmol/L,P<0.05】,SOD水平显著升高至【(0.71±0.19)U/mg,P<0.05】;模型动物肝组织Bcl-2表达量为(0.48±0.03),而Bad和c-caspase-3表达量分别为(1.50±0.18)和(1.41±0.17),分别较对照组显著降低或升高【分别为(1.76±0.18)、(0.41±0.02)和(0.28±0.01),P<0.05】,而经过蓝莓花青素处理动物肝组织Bcl-2表达显著增强,Bad和c-caspase-3表达显著减弱【分别为1.47±0.14)、(0.64±0.05)和(0.50±0.05),P<0.05]。结论 蓝莓花青素能够降低二乙基亚硝胺诱导的肝硬化大鼠肝组织氧化应激损伤,调节凋亡蛋白表达,抑制肝细胞凋亡,达到保护肝功能的作用。     

依达拉奉对大鼠急性坏死性胰腺炎的保护作用

目的:探讨自由基清除剂依达拉奉对大鼠急性坏死性胰腺炎的保护作用及其机制.方法:90只♂SD大鼠随机分为假手术组(SHAM组)、坏死性胰腺炎组(ANP组)、依达拉奉治疗组(EDA组),每组30只.SHAM组为开腹后只翻动十二指肠及胰腺后关腹;ANP组胰胆管内逆行输注1.5%脱氧胆酸钠制备急性坏死性胰腺炎模型;EDA组为ANP造模后立即尾静脉注射依达拉奉(6mg/kg).分别于术后6、12、24h处死大鼠(每个时点10只),观察胰腺病理形态改变并评分;检测血清淀粉酶、TNF-α、ET-1、sICAM-1含量;检测胰腺组织中丙二醛(MDA)含量及总超氧化物歧化酶(T-SOD)活力.结果:与ANP组比较,EDA治疗组在胰腺病理改变、血清TNF-α水平(6h:109.6ng/L±49.0ng/Lvs190.2ng/L±46.6ng/L,12h:405.4ng/L±116.3ng/Lvs559.7ng/L±203.9ng/L,24h:415.4ng/L±164.6ng/Lvs648.7ng/L±222.1ng/L,均P<0.05)、血清ET-1水平(6h:45.6ng/L±13.5ng/Lvs66.0ng/L±16.0ng/L,12h:83.5ng/L±15.4ng/Lvs96.8ng/L±23.0ng/L,24h:85.1ng/L±25.8ng/Lvs103.9ng/L±28.9ng/L),血清sICAM-1水平(6h:0.58ng/L±0.13ng/Lvs0.78ng/L±0.14ng/L,12h:0.78ng/L±0.10ng/Lvs0.94ng/L±0.12ng/L,24h:0.96ng/L±0.16ng/Lvs1.24ng/L±0.30ng/L,均P<0.05)、胰腺组织MDA含量(6h:4.22nmol/mgprot±0.40nmol/mgprotvs8.79nmol/mgprot±0.80nmol/mgprot,12h:5.90nmol/mgprot±0.51nmol/mgprotvs12.30nmol/mgprot±1.02nmol/mgprot,24h:9.10nmol/mgprot±0.84nmol/mgprotvs17.88nmol/mgprot±1.43nmol/mgprot)均有不同程度减轻(均P<0.05),T-SOD活力增强(6h:88.6U/mgprot±7.1U/mgprotvs68.8U/mgprot±10.5U/mgprot,12h:77.6U/mgprot±6.8U/mgprotvs46.0U/mgprot±8.9U/mgprot,24h:45.5U/mgprot±5.3U/mgprotvs27.8U/mgprot±4.3U/mgprot,均P<0.05);血清淀粉酶变化无显著差异.与SHAM组比较,ANP组胰腺组织病理评分、血清淀粉酶、TNF-α、ET-1、sICAM-1明显升高,胰腺组织MDA含量升高,T-SOD活力下降,差异均有统计学意义.结论:依达拉奉可以清除坏死性胰腺炎体内过量生成的氧自由基并减少炎性因子的表达,减轻胰腺组织损伤.     

活血化瘀注射液Ⅰ号预处理与缺血预处理改善肝缺血再灌注损伤

目的:研究活血化瘀注射液Ⅰ号(HHI-Ⅰ)预处理与缺血预处理(ischemic preconditioning,IP)对大鼠肝脏缺血再灌注(ischemia and reperfusion,I/R)损伤的改善作用,并比较两者的作用效果.方法:健康♂SD大鼠80只,随机分为假手术对照组(Sham组)、缺血再灌注组(I/R组)、缺血预处理组(IP组)、HHI-Ⅰ预处理组(HHI-Ⅰ组),每组20只.建立大鼠部分肝缺血模型,各组在I/R后1,3,6,24 h分别取材,测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)的水平;取左肝测组织丙二醛(MDA)、超氧化物歧化酶(SOD)的含量.I/R后1 h RTPCR检测肝组织中肿瘤坏死因子α(TNF-α)和细胞间黏附分子-1(ICAM-1)mRNA的表达,I/R后3 h行组织学观察.结果:I/R组、IP组、HHI-Ⅰ组的ALT,AST,LDH活性、MDA值和TNF-α,ICAM-1 mRNA表达水平均明显高于Sham组.IP组、HHI-Ⅰ组低于I/R组.HHI-Ⅰ组所有时间点ALT,AST,LDH明显低于IP组(ALT:2378.8±303.4 nkat/Lvs 2840.6±248.4 nkat/L;AST:2887.2±270.1nkat/L vs 4567.6±275.1 nkat/L;LDH:10550.4±710.1 nkat/L vs 12164.1±735.1 nkat/L;P均＜0.05).HHI-I组MDA值明显低于IP组(17.35±1.39 nmol/g vs 21.66±1.84 nmol/g,P＜0.05).HHI-Ⅰ组TNF-α,ICAM-1 mRNA表达水平低于IP组(TNF-α:0.54±0.06 vs 0.78±0.08;ICAM-1:0.43±0.03 vs 0.69±0.11,P均＜0.01).各组SOD值均低于Sham组(P＜0.05),IP组、HHI-Ⅰ组均高于I/R组(P＜0.05),HHI-Ⅰ组SOD(1,3,6 h)明显高于IP组(136.00±12.50 nmol/g vs 124.70±9.32 nmol/g,P＜0.05).Sham组光镜下肝小叶结构正常;I/R组肝小叶结构紊乱,肝细胞水肿变性;IP组肝细胞水肿明显,部分肝细胞变性;HHI-Ⅰ组肝小叶结构基本正常,肝细胞无明显水肿.结论:HHI-Ⅰ预处理与IP均可改善I/R对肝脏造成的损伤,前者的效果优于后者.HHI-Ⅰ的保护机制可能在于改善肝脏微循环,减轻组织缺氧状态,并通过抑制TNF-α和ICAM-1等细胞因子和细胞黏附分子的转录表达,减少肝组织中中性粒细胞的浸润.     

活血化瘀注射液I号预处理与缺血预处理改善肝缺血再灌注损伤

目的研究活血化瘀注射液Ⅰ号(HHI-Ⅰ)预处理与缺血预处理(ischemic preconditioning,IP)对大鼠肝脏缺血再灌注(ischemia and reperfusion,I/R)损伤的改善作用,并比较两者的作用效果.方法健康♂SD大鼠80只,随机分为假手术对照组(Sham组)、缺血再灌注组(I/R组)、缺血预处理组(IP组)、HHI-Ⅰ预处理组(HHI-Ⅰ组),每组20只.建立大鼠部分肝缺血模型,各组在I/R后1,3,6,24 h分别取材,测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)的水平;取左肝测组织丙二醛(MDA)、超氧化物歧化酶(SOD)的含量.I/R后1 h RTPCR检测肝组织中肿瘤坏死因子α(TNF-α)和细胞间黏附分子-1(ICAM-1)mRNA的表达,I/R后3 h行组织学观察.结果I/R组、IP组、HHI-Ⅰ组的ALT,AST,LDH活性、MDA值和TNF-α,ICAM-1 mRNA表达水平均明显高于Sham组.IP组、HHI-Ⅰ组低于I/R组.HHI-Ⅰ组所有时间点ALT,AST,LDH明显低于IP组(ALT2378.8±303.4 nkat/Lvs 2840.6±248.4 nkat/L;AST2887.2±270.1nkat/L vs 4567.6±275.1 nkat/L;LDH10550.4±710.1 nkat/L vs 12164.1±735.1 nkat/L;P均＜0.05).HHI-I组MDA值明显低于IP组(17.35±1.39 nmol/g vs 21.66±1.84 nmol/g,P＜0.05).HHI-Ⅰ组TNF-α,ICAM-1 mRNA表达水平低于IP组(TNF-α0.54±0.06 vs 0.78±0.08;ICAM-10.43±0.03 vs 0.69±0.11,P均＜0.01).各组SOD值均低于Sham组(P＜0.05),IP组、HHI-Ⅰ组均高于I/R组(P＜0.05),HHI-Ⅰ组SOD(1,3,6 h)明显高于IP组(136.00±12.50 nmol/g vs 124.70±9.32 nmol/g,P＜0.05).Sham组光镜下肝小叶结构正常;I/R组肝小叶结构紊乱,肝细胞水肿变性;IP组肝细胞水肿明显,部分肝细胞变性;HHI-Ⅰ组肝小叶结构基本正常,肝细胞无明显水肿.结论HHI-Ⅰ预处理与IP均可改善I/R对肝脏造成的损伤,前者的效果优于后者.HHI-Ⅰ的保护机制可能在于改善肝脏微循环,减轻组织缺氧状态,并通过抑制TNF-α和ICAM-1等细胞因子和细胞黏附分子的转录表达,减少肝组织中中性粒细胞的浸润.     

NF-κB对肠缺血再灌注肝损伤P-选择素表达和中性粒细胞浸润的作用

目的:探讨核转移因子-κB(NF-κB)在肠缺血再灌注肝损伤发病机制中的作用及其对P-选择素(P-selectin)表达和中性粒细胞浸润的影响．方法:Wistar大鼠24只随机分成对照(Control 组)、肠缺血再灌注(I／R组)和脯氨酸二硫代氨基甲酸酯(PDTC)治疗组(PDTC组),每组8只．I／ R和PDTC组大鼠行肠系膜上动脉夹闭1 h再灌注2 h．PDTC组于手术前1 h给予20 g／L PDTC 100 mg／kg ip．观察肝组织病理学及其肝功能变化,检测血清IL-6,肝组织匀浆超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)水平．免疫组化法观察肝组织P-selectin和NF-κB表达并采用Western blot法检测肝NF-κB的水平．结果:肠缺血再灌注诱发了肝损伤,表现为肝水肿、出血和炎性粒细胞浸润．与对照组相比,I／R组血清ALT、AST、IL-6水平明显升高 (143．16±53．02至192．31±42．09 U／L,P<0．05; 387．46±78．74至507．56±96．26 U／L,P<0．01; 22．51±6．10至42．85±7．35 ng／L,P<0．01)．肝组织SOD活性降低、MPO含量明显升高(244．87 ±25．11至173．21±16．60 U／mgprot,P<0．01; 2．36±0．56至4.32±0．77 U／g,P<0．01);肝组织的P-selectin和NF-κB表达增强．采用PDTC 预处理,与I／R组相比,肝损伤程度减轻,血清ALT(128．63±38．94 U／L)、AST(462．86± 60．84 U／L)以及IL-6(28．08±7．55 ng／L)水平明显降低(P<0．01,P<0．05,P<0．05);肝脏氧化损伤及白细胞浸润减弱,表现为肝组织SOD活性升高(253．45±25．21 U／mgprot,P<0．01)、MPO 含量降低(3．58±0．49 U／g,P<0．05),同时伴有肝组织中的P-selectin和NF-κB表达减弱．结论:肠缺血再灌注诱发肝损伤,伴有明显的中性粒细胞浸润和肝组织P-selectin的表达增强,NF-κB的活化在此损伤过程中起重要作用． PDTC通过抑制NF-κB活性对肠缺血再灌注肝损伤起保护作用．     

肝炎平对急性肝损伤大鼠细胞因子的影响

目的:探讨中药肝炎平对急性肝损害的防护作用。方法:用D-氮基半乳糖(D-GalN)制各大鼠急性肝损伤模型,检测血清丙氨酸转氮酶活性(ALT)、肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)和白细胞介素8(IL-8)浓度的变化。结果:肝损伤组ALT活性为2442.2±445.1nmol/L,TNF-α浓度为8.07±1.93ng/L,IL-6浓度为2.56±0.87ng/ml,IL-8浓度为5.78±2.12ng/ml;肝炎平组分别为1258.6±468.4nmol/L、0.63±0.27ng/L、0.52±0.13ng/ml、1.28±0.72ng/ml,各细胞因子水平均较肝损伤组明显降低(P<<0.01)。结论:肝炎平可通过对免疫机制的调节,而降低TNF-α、IL-6和IL-8等细胞因子的生成和释放。     

冠心病患者血清髓过氧化物酶和脂氧素A4水平的变化及其意义

目的:观察冠心病(CHD)患者血清髓过氧化物酶(MPO)和脂氧素A4(LXA4)水平的变化,探讨其相关的临床意义。方法:选择2013年1月至2014年9月我院的CHD患者120例为CHD组,健康体检者40例为正常对照组。CHD患者又被分为稳定型心绞痛(SAP)组(36例)、不稳定型心绞痛(UAP)组(46例)和心肌梗死(MI)组(38例);根据CT值评价的斑块性质,患者被分为钙化斑块组(27例)、混合斑块组(31例)和非钙化斑块组(62例)。比较分析各组间MPO和LXA4水平,以及MPO/LXA4比值。结果:与正常对照组比较,CHD组MPO水平[(167.2±20.4)U/L比(218.3±32.5)U/L]和MPO/LXA4[(0.78±0.08)比(1.34±0.27)]显著升高,LXA4水平[(214.6±31.3)nmol/L比(162.4±22.4)nmol/L]显著降低,P0.05或0.01。与SAP组比较,UAP组和MI组MPO[(180.4±21.6)U/L比(230.3±32.5)U/L比(238.6±44.7)U/L]水平和MPO/LXA4[(0.97±0.11)比(1.37±0.23)比(1.62±0.25)]显著升高,LXA4水平[(184.7±23.7)nmol/L比(156.3±21.2)nmol/L比(148.4±19.6)nmol/L]显著降低,且MI组MPO/LXA4显著高于UAP组,P0.05或0.01。与钙化斑块组和混合斑块组比较,非钙化斑块组MPO[(196.3±27.2)U/L比(211.2±24.6)U/L比(231.6±26.5)U/L]水平和MPO/LXA4[(1.13±0.14)比(1.26±0.16)比(1.51±0.21)]显著升高,LXA4水平[(174.3±23.4)nmol/L比(167.4±21.2)nmol/L比(154.6±19.2)nmol/L]显著降低,且混合斑块组MPO/LXA4显著高于钙化斑块组,P0.05或0.01。结论:冠心病患者存在MPO和LXA4水平的显著异常,MPO/LXA4比值更有利于患者病情程度以及动脉粥样硬化斑块稳定性的判断。     

原儿茶酸对刀豆蛋白A所致的免疫性肝损伤小鼠肝组织MDA、NO、SOD和GSH-PX表达的影响

目的 研究原儿茶酸对豆蛋白A(ConA)所致的免疫性肝损伤小鼠肝组织丙二醛(MDA)、一氧化氮(NO)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-PX)水平的影响。方法 随机将60只小鼠分为对照组、模型组、小、中、大剂量(2.5 mg.kg^-1.d^-1、5 mg.kg^-1.d^-1、10 mg.kg^-1.d^-1)原儿茶酸和(0.2 g.kg^-1.d^-1)联苯双酯处理组。在对照组和模型组给予等量生理盐水灌胃,在药物处理组分别给予不同剂量的药物灌胃,连续10 d。在末次给药1 h,一次性经尾静脉注射ConA,诱导免疫性肝损伤模型。分别检测血清白介素-4(IL-4)、IL-6、肿瘤坏死因子-α(TNF-α)和肝组织匀浆MDA、NO、SOD和GSH-PX活性。结果 不同剂量原儿茶酸和联苯双酯处理组动物肝、脾指数显著降低,血清ALT和AST水平显著降低,血清IL-4、IL-6和TNF-α水平显著降低(P<0.05);模型组肝匀浆MDA和NO水平分别为(5.2±0.5)nmol/mg和(8.0±0.9)μmol/L,经小、中、大剂量原儿茶酸处理后,分别降至【(4.7±0.4)nmol/mg、(4.3±0.3)nmol/mg和(3.9±0.3)nmol/mg及(6.8±0.8)μmol/L、(6.2±0.7)μmol/L和(5.8±0.7)μmol/L,P<0.05】;模型组肝匀浆SOD和GSH-PX水平分别为(59.4±3.6)U/mg和(85.2±9.6)U/mg,经小、中、大剂量原儿茶酸处理后,分别升高至【(74.2±4.4)U/mg、(85.2±5.3)U/mg和(99.2±5.9)U/mg及(107.3±13.4)U/mg、(115.2±12.8)U/mg和(139.3±12.9)U/mg,P<0.05】。结论 原儿茶酸可以减轻ConA引起的小鼠免疫性肝损伤,可能是通过提高了肝组织内源性抗氧化酶活力,增强了对氧自由基的清除能力有关。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.